Most patients diagnosed with oral squamous cell carcinoma (OSCC) present with locally advanced stages, which are typically associated with poor outcomes. Although immunotherapy offers potential improvements in patient survival, its efficacy is hampered by low response rates. The microbiome is widely involved in tumor immunity and may play a role in immunotherapy. This study aimed to investigate the potential association between the oral (salivary) microbiome and immunotherapy response in patients with OSCC. Salivary metagenome sequencing was performed on 47 patients with OSCC undergoing neoadjuvant immunotherapy (NAIT) in a clinical trial (NCT04649476). Patients were divided into responders and nonresponders based on their pathological responses. The results showed that the species richness of the salivary microbiome was lower in the nonresponders before NAIT than in the responders. Differential analysis revealed that nonresponders exhibited a lower relative abundance of 34 bacterial species and a higher relative abundance of 4 bacterial species. Notably, low levels of Eubacterium infirmum, Actinobaculum, and Selenomas (EAS) in the saliva may be associated with the nonresponse of patients with OSCC to NAIT. A nomogram based on EAS was developed and validated to determine the efficacy of NAIT. The area under the curve for the training cohort was 0.81 (95% confidence interval, 0.66 to 0.81). Quantitative polymerase chain reaction confirmed that low levels of salivary EAS effectively identified nonresponders to NAIT. Furthermore, the low abundance of salivary EAS was closely correlated with a low density of intratumoral CD4+, CD14+, CD68+, and FOXP3+ cells. Metabolic functional annotation revealed numerous biosynthetic processes associated with EAS that were more active in responders. In summary, this study provides valuable data resources for the salivary microbiome and reveals that nonresponders have different salivary microbiome profiles than responders do before NAIT. Low salivary EAS levels can serve as potential biomarkers for distinguishing nonresponders from responders.

中文翻译：

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唾液微生物组与 OSCC 新辅助免疫治疗反应相关


大多数诊断为口腔鳞状细胞癌 (OSCC) 的患者均已处于局部晚期，这通常与不良预后相关。尽管免疫疗法可以提高患者的生存率，但其疗效因反应率低而受到阻碍。微生物组广泛参与肿瘤免疫，并可能在免疫治疗中发挥作用。本研究旨在调查 OSCC 患者口腔（唾液）微生物组与免疫治疗反应之间的潜在关联。在一项临床试验 (NCT04649476) 中，对 47 名接受新辅助免疫治疗 (NAIT) 的 OSCC 患者进行了唾液宏基因组测序。根据病理反应将患者分为有反应者和无反应者。结果表明，NAIT 之前无反应者的唾液微生物组物种丰富度低于反应者。差异分析显示，无应答者表现出 34 种细菌的相对丰度较低，而 4 种细菌的相对丰度较高。值得注意的是，唾液中软弱真杆菌、放线杆菌和硒瘤 (EAS) 水平低可能与 OSCC 患者对 NAIT 无反应有关。开发并验证了基于 EAS 的列线图以确定 NAIT 的功效。训练队列的曲线下面积为 0.81（95% 置信区间，0.66 至 0.81）。定量聚合酶链反应证实，低水平的唾液 EAS 可以有效识别对 NAIT 无反应的人。此外，唾液 EAS 的低丰度与瘤内 CD4+、CD14+、CD68+ 和 FOXP3+ 细胞的低密度密切相关。 代谢功能注释揭示了许多与 EAS 相关的生物合成过程，这些过程在反应者中更为活跃。总之，这项研究为唾液微生物组提供了宝贵的数据资源，并揭示了无应答者与 NAIT 前应答者相比具有不同的唾液微生物组特征。低唾液 EAS 水平可以作为区分无反应者和反应者的潜在生物标志物。